Herpes simplex virus-1 fluidizes the nucleus enabling condensate formation.

Area of Science:

• Cellular biophysics
• Virology
• Molecular biology

Background:

• Cellular molecular processes are significantly affected by the physical properties of the cell's interior, particularly the nucleus.
• The mechanisms governing these biophysical properties and their impact on cellular functions are not well understood.

Purpose of the Study:

• To investigate whether viruses alter nuclear biophysical properties to enhance their survival and replication.
• To determine the role of herpes simplex virus 1 (HSV-1) in modulating nuclear properties.

Main Methods:

• Assessing changes in nuclear mesoscale fluidity upon HSV-1 infection.
• Investigating the effect of the HSV-1 protein ICP4 on nuclear condensate formation.
• Evaluating the impact of altered nuclear fluidity on viral replication and infectious virus production.

Main Results:

• HSV-1 infection was found to increase the mesoscale fluidity of the nucleus.
• The viral protein ICP4 was identified as the cause of nuclear fluidization and promoted the growth of synthetic nuclear condensates.
• Reduced nuclear fluidity inhibited the formation of viral replication compartment condensates and decreased infectious virus yield.

Conclusions:

• HSV-1 protein ICP4 increases nuclear fluidity, facilitating the formation of essential condensates for viral life cycle progression.
• Altering nuclear fluidity is a key strategy for HSV-1 to overcome physical barriers within the nucleus, promoting viral replication.